佐田 尚宏

Aim: Peritoneal metastases (PM) frequently occur in patients with gastric cancer and result in a poor prognosis. Exosomes play pivotal roles in tumor metastasis through the transfer of microRNAs (miRNAs). We examined the exosomal miRNA profile in peritoneal fluids to identify novel biomarkers to reflect tumor burden in the peritoneum. Methods: Exosomes were isolated from peritoneal fluids of patients of gastric cancer with macroscopic (P1) or microscopic (P0CY1) peritoneal metastasis (PM) and comprehensive miRNA expression analysis was carried out. Expressions of candidate miRNAs were then validated in all 58 samples using TaqMan Advanced miRNA Assays. Results: In initial screening, we carried out comprehensive analysis of exosomal miRNA using peritoneal fluids from 11 and 14 patients with or without PM, respectively, and identified 11 dysregulated miRNAs in PM (+) samples. Validation analysis showed that four miRNAs (miR-21-5p, miR-92a-3p, miR-223-3p, and miR-342-3p) were significantly upregulated in 12 PM (+) samples, and their expression levels showed positive correlation with peritoneal cancer index. In contrast, miR-29 family were all downregulated in patients with PM (+) samples. Moreover, in 24 patients with pT4 tumor, miR-29 at gastrectomy tended to be lower in six patients with peritoneal recurrence with significant differences in miR-29b-3p (P = .012). Conclusion: Expression pattern of miRNAs in peritoneal exosomes well reflects the tumor burden in the peritoneal cavity and could be a useful biomarker in the treatment of PM.

INTRODUCTION: Gastric adenocarcinomas with low grade atypia may be difficult to diagnose as gastric cancer by preoperative biopsy. We report an extremely well-differentiated adenocarcinoma (EWDA) of the stomach which appeared like a submucosal tumor diagnosed by preoperative endoscopic submucosal dissection. PRESENTATION OF CASE: A 70-year-old male was referred with a 3-month history of a submucosal-appearing lesion in the gastric wall found on endoscopy. Biopsies of the lesion were performed and were inconclusive for neoplasia. Endoscopic ultrasonography showed a low echoic tumor growing into the fourth layer of the gastric wall. It was difficult to identify the tumor by repeat biopsy. Endoscopic submucosal dissection of the lesion was performed and revealed adenocarcinoma, and laparoscopic total gastrectomy was performed. Histopathologic evaluation showed that the tumor was stage IIA (T3N0M0). There is no recurrence 12 months after resection. DISCUSSION: Gastric EWDAs are rare lesions, accounting for 0.6% of all gastric cancers. It is difficult to diagnose gastric EWDA especially if it appears like a submucosal tumor. This lesion was finally diagnosed by endoscopic submucosal dissection. CONCLUSION: Endoscopic submucosal dissection may facilitate establishing the preoperative diagnosis of a tumor thought to be a gastric EWDA based on its endoscopic appearance and pathological findings.

A 68-year-old male was referred with dysphagia. Endoscopic findings showed circular stenosis with a protruding mass in the lower esophagus. Biopsy showed adenocarcinoma and there was no evidence of distant metastases. A subtotal esophagectomy was performed. The resected specimen revealed a mixed neuroendocrine carcinoma with adenocarcinoma. The adenocarcinoma component was on the surface of the tumor and the neuroendocrine component invaded the deeper portion. Immunohistochemically, the neuroendocrine carcinoma component stained positive for cytokeratin 7 and cytokeratin 20, suggesting that the neuroendocrine carcinoma originated from the adenocarcinoma. The adenocarcinoma component stained positive for MUC2, which suggests that the adenocarcinoma component originated from Barrett's epithelium. Taken together, the neuroendocrine carcinoma may have originated from Barrett's epithelium. A metastasis to the liver was found 2 months after the surgical resection. Chemotherapy was administered, but there was no response. Most esophageal neuroendocrine carcinomas are accompanied by adenocarcinoma or squamous cell components, suggesting that these carcinomas originate from pluripotent cells in squamous or Barrett's epithelium. Appropriate chemotherapy for these lesions should be considered based on the cell of origin.

PURPOSE: Advances in interventional radiology (IVR) treatment have notably improved the prognosis of hepatic vein (HV) and portal vein (PV) complications following pediatric living donor liver transplantation (LDLT); however, graft failure may develop in refractory cases. Although endovascular stent placement is considered for recurrent stenosis, its indications are controversial. METHODS: We enrolled 282 patients who underwent pediatric LDLT in our department from May 2001 to September 2016. RESULTS: 22 (7.8%) HV complications occurred after LDLT. Recurrence was observed in 45.5% of the patients after the initial treatment, and 2 patients (9.1%) underwent endovascular stent placement. The stents were inserted at 8 months and 3.8 years following LDLT, respectively. After stent placement, both patients developed thrombotic obstruction and are currently being considered for re-transplantation. 40 (14.2%) PV complications occurred after LDLT. Recurrence occurred in 27.5% of the patients after the initial treatment, and 4 patients (10.0%) underwent endovascular stent treatment. The stents of all the patients remained patent, with an average patency duration of 41 months. CONCLUSION: Endovascular stent placement is an effective treatment for intractable PV complications following pediatric LDLT. However, endovascular stent placement for HV complications should be carefully performed because of the risk of intrastent thrombotic occlusion and the possibility of immunological venous injury.

BACKGROUND: Intestinal ischemia/reperfusion (I/R) injury is a life-threatening complication that leads to inflammation and remote organ damage. However, the underlying mechanism is not yet fully understood. Toll-like receptor 5 (TLR5) is highly expressed in mucosa and recognizes flagellin, the main component of the bacterial flagella. Here, we investigated the role of TLR5 in inflammation and tissue damage after intestinal I/R injury using TLR5-deficient mice. METHODS AND RESULTS: Intestinal levels of TLR5 mRNA and flagellin protein were elevated in wild-type mice subjected to intestinal I/R. Although TLR5 deficiency had no effect on intestinal flagellin levels, it significantly attenuated intestinal injury and inflammatory responses after intestinal I/R. TLR5 deficiency also markedly improved survival in mice after intestinal I/R injury. In wild-type mice, intestinal I/R injury induced remote organ damage, particularly in the lung, which was attenuated by TLR5 deficiency. Furthermore, TLR5 deficiency prevented lung inflammatory responses and vascular permeability after intestinal I/R injury. CONCLUSION: These findings demonstrate a novel role of TLR5 and provide new insights into the mechanism underlying inflammation and tissue damage after intestinal I/R injury.

BACKGROUND: Primary sarcoma of the breast is rare. Surgery has been the only curative treatment available. Recently, neoadjuvant chemotherapy including anthracycline/ifosfamide has been reported effective for patients with high-risk sarcomas in a prospective trial. CASE PRESENTATION: A 52-year-old Japanese woman presented with a mass in her left breast. The 10 cm tumor was fixed to her chest wall on examination. A skin biopsy was performed which showed leiomyosarcoma. Neoadjuvant chemotherapy was given and the tumor became mobile. A mastectomy and axillary dissection were performed with surgically negative margins. After neoadjuvant chemotherapy, the amount of necrosis was profoundly influenced by chemotherapy, and the histological effect of neoadjuvant chemotherapy was assessed in reference to pre-neoadjuvant chemotherapy magnetic resonance imaging. CONCLUSION: In contrast to many other cancers, the evaluation of various treatments and of the histological effect of neoadjuvant chemotherapy for sarcoma has been difficult due to the rarity of these tumors. We report the case of a patient with a breast sarcoma, treated with neoadjuvant chemotherapy and discuss the appropriate pathological evaluation and therapeutic management.

Gastrointestinal stromal tumors (GIST) in patients under 18 years of age are classified as pediatric GIST. Pediatric GIST are extremely rare, and there are no reports of laparoscopic-endoscopic cooperative surgery for these lesions. We report the use of non-exposed endoscopic wall-inversion surgery as a laparoscopic-endoscopic cooperative surgery-related procedure for the treatment of a pediatric GIST. The case involved a 17-year-old male patient who presented with anemia and was found to have a bleeding gastric tumor. The tumor was resected transorally using the non-exposed endoscopic wall-inversion surgery technique. No gene mutation of c-Kit or Platelet-Derived Growth Factor Receptor α (PDGFRα) was found, and the final pathological diagnosis was epithelial-type GIST due to a succinate dehydrogenase abnormality. Follow-up included a CT scan every 4 months. No recurrence has occurred to date.

OBJECTIVE: Mucin1 (MUC1), a member of the mucin family, is a glycoprotein which is often expressed in malignant cells. However, the expression and function of MUC1 in human duodenal adenocarcinoma (DAC) has not yet been characterized because of its low frequency. Here, we examined the functional roles of core protein (MUC1-C) in DAC. MATERIALS AND METHODS: Using a human duodenal cancer cell line, HuTu80, proliferation, migration, invasion, ALDH activity was assessed by cell counting kit-8, scratch wound healing, matrigel invasion, and ALDEFUOR assays, respectively. The function of MUC1 protein was evaluated with knockdown using specific siRNA as well as anti-MUC1-C peptide, GO203. MUC1 expression in human DAC was evaluated immunohistochemically in surgically resected tumors. RESULTS: The positive expression of MUC1 in HuTu80 was confirmed by RT-PCR and flow cytometry. In vitro cell growth was inhibited by the addition of 50-100 μM GO203 as well as treatment with siRNA for MUC1-C. Silencing of MUC1-C also significantly reduced migration, invasion, ALDH activity. Local injection of GO-203 (14 mg/kg) significantly suppressed the growth of subcutaneous HuTu80 tumors in nude mice. Immunohistochemically, MUC1 was strongly detected in seven DAC cases, but not in 11 others. The outcome of patients with high MUC1 expression was significantly worse than those without MUC1 expression. CONCLUSIONS: These results suggest that MUC1 is functionally associated with the malignant potential of DAC and could be a novel therapeutic target for this rare tumor.

BACKGROUND: Abnormally high estimated glomerular filtration rates (eGFRs) are associated with endothelial dysfunction and frailty. Previous studies have shown that low eGFR is associated with increased morbidity, but few reports address high eGFR. The purpose of this study is to evaluate the association of high eGFR with surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. METHODS: We identified patients who underwent elective surgery for gastrointestinal malignancies from 2005 to 2015 in the American College of Surgeons National Surgical Quality Improvement Program database. We evaluated associations of eGFR with surgical outcomes by Cox or logistic models with restricted cubic spline functions, adjusting for case mix variables (i.e. age, gender, race and diabetes). RESULTS: The median eGFR is 83 (interquartile range 67-96) mL/min/1.73 m2. Thirty-day mortality was 1.9% (2555/136 896). There is a U-shaped relationship between eGFR and 30-day mortality. The adjusted hazard ratios (95% confidence intervals) for eGFRs of 30, 60, 105 and 120 mL/min/1.73 m2 (versus 90 mL/min/1.73 m2) are 1.73 (1.52-1.97), 1.00 (0.89-1.11), 1.42 (1.31-1.55) and 2.20 (1.79-2.70), respectively. Similar associations are shown for other surgical outcomes, including return to the operating room and postoperative pneumonia. Subgroup analyses show that eGFRs both higher and lower than the respective medians are consistently associated with a higher risk of adverse outcomes across age, gender and race. CONCLUSIONS: High and low eGFRs are associated with more adverse surgical outcomes in patients undergoing surgery for gastrointestinal malignancies. The eGFR associated with the lowest postoperative risk is approximately at the median eGFR of a given population.

INTRODUCTION: Transverse colon resection is one of the most difficult laparoscopic procedures because of anatomic hazards such as variations in the mesenteric vascular anatomy and the complex structure of organs and surrounding membranes. METHODS: We evaluated the short-term surgical outcomes of laparoscopic transverse colon resection using a creative approach. This approach included preoperative surgical simulation using virtual surgical anatomy by CT, a four-directional approach to the mesentery, and 3-D imaging during laparoscopic surgery. RESULTS: A total of 45 consecutive patients who underwent laparoscopic resection for transverse colon cancer from June 2013 to December 2017 were enrolled in this study. All procedures were completed safely, with minor postoperative complications, including two patients with anastomotic stenosis, two with intra-abdominal phlegmon, one with delayed gastric emptying, and one with pneumonia, all treated non-operatively. There were no conversions to open resection. Operation time was 203 min (range, 125-322 min), and the estimated blood loss during surgery was 5 mL (range, 0-370 mL). The mean postoperative hospital stay was 10 days (range, 7-21 days), and no patients required readmission. CONCLUSION: Short-term surgical outcomes after laparoscopic transverse colon resection demonstrated that this creative approach was safe and feasible. The four-directional approach to the meso-transverse attachment combined with preoperative radiological simulation can facilitate laparoscopic transverse colon surgery.

Bile duct cancer is known to contain numerous fibroblasts, and reported to recruit cancer- associated fibroblasts by secreting platelet-derived growth factor-D (PDGF-D) which needs serine proteases, such as matriptase, to behave as a ligand. However, their expression pattern, and prognostic value have not been clarified. In this study, we investigated the clinicopathological significance of PDGF-D and matriptase expression in patients with extrahepatic bile duct cancer. The samples were obtained from 256 patients who underwent the surgical resection between 1991 and 2015, and the expression levels of PDGF-D and matriptase were evaluated immunohistochemically. Staining intensities and distribution were scored, and finally classified into low and high expression groups in cancer cells and stroma respectively. High expression of matriptase in the cancer stroma was detected in 91 tumors (40%). The high stromal matriptase expression was significantly associated with shorter recurrence-free survival (RFS) and overall survival (OS) (P = 0.0027 and 0.0023, respectively). Multivariate analyses also demonstrated that the stromal matriptase expression level was an independent influential factor in RFS (P = 0.0050) and OS (P = 0.0093). Our findings suggest that the high stromal matriptase expression was strongly associated with tumor progression, recurrence and poor outcomes in patients with extrahepatic bile duct cancer.

INTRODUCTION: Immune thrombocytopenic purpura is an acquired thrombocytopenia. Preoperative management of thrombocytopenia is important in patients with gastric cancer. Partial splenic embolization can be effective for patients with thrombocytopenia, but could lead to ischemic necrosis of the remnant stomach when performing subtotal gastrectomy with splenectomy. PRESENTATION OF CASE: The patient is an 84-year old woman evaluated for anemia. Endoscopy revealed an advanced gastric cancer with bleeding. The patient also had immune thrombocytopenic purpura with a platelet count <50,000/μL. Administration of platelets did not increase the platelet count. Partial splenic embolization was performed followed by administration of high-dose immunoglobulin. The platelet count was over 50,000/μL preoperatively. The patient underwent combined subtotal gastrectomy and splenectomy, followed by an uneventful course. DISCUSSION: Patients with immune thrombocytopenic purpura and advanced gastric cancer can have anemia. Partial splenic embolization has been used to treat patients with refractory immune thrombocytopenic purpura as an alternative to splenectomy. Preoperative partial splenic embolization and high-dose immunoglobulin therapy resulted an increased platelet count in this patient. Elderly patients with gastric cancer have a high risk of postoperative complications. Patients with gastric cancer undergoing total gastrectomy have an impaired postoperative quality of life compared to those who undergo subtotal gastrectomy. We performed a subtotal gastrectomy and splenectomy as a function-preserving operation, completed safely by maintaining blood flow to the remnant stomach. CONCLUSION: Partial splenic embolization is effective for patients with immune thrombocytopenic purpura and gastric cancer. Combined subtotal gastrectomy and splenectomy is achieved by preserving blood flow to the remnant stomach.

INTRODUCTION: Gastric hyperplastic polyps are common stomach lesion and these polyps are generally benign. However, they can undergo malignant transformation. Most reported cases of malignant transformation of gastric hyperplastic polyps have been to well or moderately differentiated adenocarcinoma, and those transformed into poorly differentiated adenocarcinoma are extremely rare. No case has been reported that has changed to diffuse type adenocarcinoma with lymphatic invasion. PRESENTATION OF CASE: A 48-year-old woman presented with worsening anemia. A polyp was seen in the gastric cardia seven years prior to presentation. Helicobacter pylori infection was also found at that time. She underwent upper gastrointestinal endoscopy and biopsy of the polyp revealed signet ring cell carcinoma. Total gastrectomy was performed due to concern about possible invasion into the submucosal layer and there was no evidence of distant metastases. Histologic examination revealed both poorly differentiated adenocarcinoma and signet ring cell carcinoma surrounded by hyperplastic epithelium at the head of the polyp. Lymphatic invasion was also found, and malignant cells were limited to the mucosa. DISCUSSION: Gastric hyperplastic polyps are commonly associated with chronic gastritis which is related to Helicobacter pylori infections. Gastric hyperplastic polyps are generally benign and rarely undergo malignant transformation to adenocarcinoma with differentiated histology. The gastric hyperplastic polyp in this patient transformed to poorly differentiated adenocarcinoma with lymphatic invasion. CONCLUSION: Even small polyps may become poorly differentiated adenocarcinoma with invasion, so close follow-up or endoscopic resection are recommended as well as eradication of Helico Pylori infection when appropriate.

BACKGROUND: Thymomas are typically slow-growing tumors and AB type thymomas are considered no/low risk tumors with a better prognosis. Extra-thoracic metastases are extremely rare. To the best of our knowledge, no patient with an isolated splenic metastasis from a thymoma has been reported. We report a patient who underwent laparoscopic splenectomy for a slow-growing, isolated splenic metastasis, eight years after thymectomy. CASE PRESENTATION: The patient is a 78-year-old man. Eight years previously, the patient underwent extended thymectomy and postoperative radiation therapy for a thymoma. Five years after thymectomy, a nodule appeared in the spleen, and the lesion enlarged gradually for three years thereafter. The patient was referred for further examination and treatment. Computed tomography scan showed a sharply circumscribed 50 mm tumor slightly hypodense and heterogeneous lesion in the spleen. On T2-weighted images on Magnetic Resonance Imaging, the tumor had high intensity, equivalent to or slightly lower than that on T1-weighted images, and no decrease on diffusion-weighted images. The tumor was multinodular and showed a low-signal spoke-wheel sign in the margin, enhanced gradually in the dynamic study. Positron emission tomography-CT scan, showed relatively low accumulation. Surgical resection was undertaken, and pathological examination showed metastatic thymoma. The patient is without recurrence and has no other symptoms three years after splenectomy. CONCLUSIONS: This is the first report of an isolated splenic metastasis from a thymoma. Further cases are needed to standardize this surgery for such lesions.

Little is known concerning the prognostic significance of the degree of lymphatic vessel invasion in pancreatic head cancer. To address this gap in knowledge, we retrospectively examined 60 patients with locally advanced, surgically resectable pancreatic head cancer who underwent pancreaticoduodenectomy and lymph node (LN) dissection.All cases were histopathologically diagnosed as ductal adenocarcinoma, stage II (25 pT3N0 cases, 35 pT3N1 cases). The following variables were investigated: age; sex; neoadjuvant therapy; adjuvant therapy; tumor size; tumor grade; invasion into the serosa, retropancreatic tissue, duodenum, bile duct, portal venous system and perineural area; cut margins; LN metastasis; and the number of invaded lymphatic vessels (LVI-score).Univariate analysis demonstrated that LN metastasis and an LVI-score ≥5 were significantly associated with poor disease-free survival. Multivariate Cox regression analysis confirmed that LN metastasis and an LVI-score ≥7 were significantly associated with poor disease-free survival. Additionally, LVI-scores ≥9 and ≥10 were comparable to or surpassed the significance of LN metastasis based on the hazard ratio. Univariate analysis demonstrated that tumor size >30 mm, duodenal invasion, LN metastasis and an LVI-score ≥2 were significantly associated with poor overall survival. Multivariate Cox regression analysis confirmed that LN metastasis and LVI-scores ≥9 and ≥10 were significantly associated with poor overall survival, and an LVI-score ≥10 was comparable to or surpassed the significance of LN metastasis based on the hazard ratio.Our study strongly suggests that a high degree of lymphatic vessel invasion is associated with a poor prognosis in patients with locally advanced, surgically resectable pancreatic head cancer.

BACKGROUND: Whether non-colorectal non-neuroendocrine liver metastasis (NCNNLM) should be treated surgically remains unclear. METHODS: Data regarding 1,639 hepatectomies performed between 2001 and 2010 for 1,539 patients with NCNNLM were collected from 124 institutions. Patient characteristics, types of primary tumor, characteristics of liver metastases, and post-hepatectomy outcomes were analyzed. RESULTS: The five most frequent primary tumors were gastric carcinoma (540 patients [35%]), gastrointestinal stromal tumor (204 patients [13%]), biliary carcinoma (150 patients [10%]), ovarian cancer (107 patients [7%]), and pancreatic carcinoma (77 patients [5%]). R0/1 hepatectomy was achieved in 90% of patients, with 1.5% in-hospital mortality rate. Overall and disease-free survival rates of 1,465 patients included in survival analysis were 41% and 21%, respectively, at 5 years, and 28% and 15%, respectively, at 10 years. Five-year survival associated with the five frequent primary tumors were 32%, 72%, 17%, 52%, and 31%, respectively, and factors predictive of a poor outcome differed by the primary tumor type. CONCLUSIONS: Our data indicated that hepatectomy is safe for NCNNLM and that patient prognoses vary depending on the type of primary tumors. Indications for hepatectomy should be determined with reference to survival rates and risk factors specific to each of the various types of primary tumor.

INTRODUCTION: Laparoscopic lateral pelvic lymph node dissection (LPLD) is technically challenging because of the complicated anatomy of the pelvic wall. To overcome this difficulty, we introduced preoperative 3-D simulation. The aim of the study is to investigate the usefulness of preoperative 3-D simulation for the safe conduct of laparoscopic LPLD for rectal cancer. METHODS: After undergoing colonoscopy, patients were brought to the radiology suite where multi-detector row CT was performed. Three-dimensional images were constructed at a workstation and showed branches of the iliac artery and vein, ureter, urinary bladder, and enlarged lymph nodes. All members of the surgical team participated in preoperative simulation using the 3-D images. RESULTS: A total of 10 patients with advanced lower rectal cancer and enlarged lateral pelvic lymph nodes underwent laparoscopic unilateral LPLD after total mesorectal excision, tumor-specific mesorectal excision, or total proctocolectomy. Four of the 10 patients (40%) had variations in pelvic vascular anatomy. The median operative time for unilateral LPLD was 91 min (range, 66-142 min) and gradually declined, suggesting a good learning curve. The median number of lateral pelvic lymph nodes harvested was nine (range, 3-16). The median estimated blood loss was 13 mL (range, 10-160 mL). No conversion to open surgery or intraoperative complications occurred. No patient had major postoperative complications. CONCLUSION: Preoperative 3-D simulation may be useful for the safe conduct of laparoscopic LPLD, especially for surgeons with limited prior experience.

Activated neutrophils release neutrophil extracellular traps (NETs), which can capture and destroy microbes. Recent studies suggest that NETs are involved in various disease processes, such as autoimmune disease, thrombosis, and tumor metastases. Here, we show a detailed in vitro technique to detect NET activity during the trapping of free tumor cells, which grow after attachment to NETs. First, we collected low density neutrophils (LDN) from postoperative peritoneal lavage fluid from patients who underwent laparotomies. Short-term culturing of LDN resulted in massive NET formation that was visualized with green fluorescent nuclear and chromosome counterstain. After co-incubation of human gastric cancer cell lines MKN45, OCUM-1, and NUGC-4 with the NETs, many tumor cells were trapped by the NETs. Subsequently, the attachment was completely abrogated by the degradation of NETs with DNase I. Time-lapse video revealed that tumor cells trapped by the NETs did not die but instead grew vigorously in a continuous culture. These methods may be applied to the detection of adhesive interactions between NETs and various types of cells and materials.

BACKGROUND: The genesis of the "complex type" classification of pancreaticobiliary maljunction (PBM) is unclear, and the pancreaticobiliary anatomy is also varied according to each case. We encountered a patient with PBM and incomplete pancreatic divisum (PD). We herein discussed about the embryological etiology of pancreaticobiliary system predicted from PBM with incomplete PD. CASE PRESENTATION: A 67-year-old man was found to have a dilatation of the common bile duct (CBD) during a medical examination at 62 years of age. The dilatation of the CBD subsequently progressed, and he was admitted to our hospital for surgical treatment. Magnetic resonance cholangiopancreatography revealed a dilatation from the common hepatic duct to the middle bile duct with PBM. Endoscopic retrograde cholangiopancreatography from the papilla of Vater revealed the pancreatic main duct via the pancreatic branch duct, and PBM with dilatation of the CBD and incomplete PD were revealed. We performed an extrahepatic bile duct resection and hepaticojejunostomy because of high risk of malignant transformation. Taping and transection of the bile duct without dilatation on the pancreatic side were performed, and thereafter, two orifices of the common channel and ventral pancreatic duct were ligated. The level of amylase in the bile was 7217 IU/L, and a histological examination of the CBD showed an inflammatory change of CBD, not a malignant transformation. CONCLUSION: It is somewhat easy to identify the pancreatobiliary anatomy when the cause of embryology of both PBM and PD is thought to be an abnormal embryology of the ventral pancreas.

We report three cases of colonoscope incarceration in a left inguinal hernia. In the first case, colonoscopy could be successfully performed with manual compression. The colonoscope could not be inserted in the other two cases. It is important to obtain a careful history and physical examination before colonoscopy. The scope must be carefully removed in patients with an inguinal hernia.

RATIONALE: Although systemic lupus erythematosus (SLE) can be complicated by various gastrointestinal tract diseases, it is rarely associated with lupus enteritis and protein-losing enteropathy (PLE). We report here the successful surgical treatment of lupus enteritis and therapy-resistant and refractory PLE in a patient with SLE. We also provide a review of relevant literature. PATIENT CONCERNS: A 16-year-old girl presenting with polyarthritis, malar rash, and palmar erythema was indicated for steroid therapy on the basis of positive results for antinuclear, anti-Smith, and antiphospholipid antibodies, which confirmed the diagnosis of SLE. During the course of steroid therapy, the patient developed acute abdomen and hypoalbuminemia. DIAGNOSES: Computed tomography and Tc-labeled human serum albumin scintigraphy revealed abnormal findings, and a diagnosis of lupus enteritis and PLE was made. Steroid treatment was continued but no significant improvement was observed, and the patient was referred and admitted to our hospital. Double-balloon enteroscopy revealed multiple ischemic stenoses and mucosal necroses in the small intestine, suggesting that PLE was associated with ischemic enteritis due to antiphospholipid syndrome. The patient received steroids, immunosuppressive drugs, and antithrombotic therapy, with no improvement in symptoms. Thus, the disease was judged to be refractory and resistant to medical therapy, and the patient was indicated for surgical treatment. INTERVENTIONS: Partial small intestinal resection was performed by removing the segment of the small intestine presenting PLE lesions, and a double-end ileostomy was created. OUTCOMES: Multiple stenotic lesions were confirmed in the resected segment. Histopathology evaluation revealed marked inflammatory cell infiltration in the intestinal tract wall and recanalization of the vessels, suggesting a circulatory disorder caused by vasculitis and antiphospholipid syndrome. Postoperatively, the clinical course was good. Serum albumin levels and body weight increased as nutritional status improved significantly. Secondary enteroenterostomy with ileostomy closure could be performed at 2 months after the initial surgery. LESSONS: Timely surgical treatment can be successful in managing therapy-resistant and refractory PLE in patients with SLE.

BACKGROUND: We evaluated the efficacy and safety of a modified FOLFIRINOX regimen for chemotherapy-naïve patients with metastatic pancreatic cancer. METHODS: Patients with untreated metastatic pancreatic cancer (MPC) received modified FOLFIRINOX (intravenous oxaliplatin 85 mg/m2, irinotecan 150 mg/m2, 5-FU infusion 2400 mg/m2 over 46 h, no bolus 5-FU). The primary endpoints were overall survival and the incidence of grade 3 or higher neutropenia. No patients received prophylactic pegfilgrastim. RESULTS: Sixty-nine pts. were enrolled from 39 institutions in Japan. The median overall survival was 11.2 months [95% confidence interval (CI) 9.0-]. The median progression-free survival was 5.5 months (95% CI 4.1-6.7). The response rate was 37.7% (95% CI 26.3-50.2), and the disease control rate was 78.3% (95% CI 66.7-87.3). The incidence of grade 3 or higher neutropenia was 47.8%. Serious adverse events occurred in six patients (8.7%). All AE proportions were less than those in the previous Japanese full-dose phase II study. One patient died due to interstitial pneumonia related to treatment. CONCLUSION: This is the first prospective study of modified FOLFIRINOX in Asia. Modified FOLFIRINOX in this study has an improved safety profile with maintained efficacy in MPC without prophylactic pegfilgrastim.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is a primary pancreatic ductal epithelial neoplasm with the potential to develop into an invasive adenocarcinoma. This study aimed to investigate the clinicopathologic and prognostic significance of four potential biomarkers for the preoperative evaluation of patients with IPMN. MATERIALS AND METHODS: Clinicopathologic materials from 104 patients with IPMN who underwent surgical resection at Jichi Medical University Hospital were analyzed. IPMNs (110 lesions in total) were histologically classified into low-grade IPMN (Group 1; n = 68), high-grade IPMN (Group 2; n = 16), or IPMN with an associated invasive carcinoma (Group 3; n = 26). We evaluated the immunohistochemical expression of MUC13, AGR2, FUT8, and FXYD3, which were previously reported to be overexpressed in pancreatic ductal adenocarcinoma. RESULTS: The expression of MUC13 was more common in Group 3 compared with groups 1 and 2 (p < 0.001) and was associated with poor prognosis (p = 0.004). The expression of MUC13 was not associated with age, sex, tumor location, histological subtype, lymphatic or vascular invasion, or neural invasion. In most cases of IPMN, the loss of expression of AGR2 appeared to show an association with tumor recurrence and poorly differentiated histology of invasive carcinoma; however, this association was not statistically significant. The expressions of FUT8 and FXYD3were not associated with the clinicopathological features of IPMNs. CONCLUSIONS: The results suggest that MUC13 overexpression and loss of expression of AGR2 may predict the progression of IPMN and an unfavorable prognosis in patients with IPMN.

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Atypical femoral fractures (AFFs) occur in both osteoporosis patients and cancer patients who receive long-term bisphosphonate treatment. Denosumab offers an alternative approach for the treatment of bone metastases. We describe a 59-year-old woman with a history of breast carcinoma and bone metastasis who was prescribed denosumab for 4 years. The patient had no history of any prior bisphosphonate use. Bone scintigraphy showed an abnormal uptake in the right femur, which was confirmed as an impending AFF or atypical femoral stress reaction. In oncological patients receiving long-term denosumab, AFF should be included as a differential diagnosis for focal femoral findings.

Oxytocin (OT) is a 9-amine neuropeptide that plays an essential role in mammalian labor, lactation, maternal bonding, and social affiliation. OT has been reported to exert an analgesic effect in both humans and animals, and the results of certain animal experiments have shown that the analgesic effect of OT is partially blocked by opioid receptor antagonists. To investigate the relationship between OT and μ opioid receptor (MOR), we evaluated how OT affects MOR in vitro by performing an electrical impedance-based receptor biosensor assay (CellKey™ assay), an intracellular cAMP assay, and a competitive receptor-binding analysis by using cells stably expressing human MOR and OT receptor. In both the CellKey™ assay and the intracellular cAMP assay, OT alone exerted no direct agonistic effect on human MOR, but treatment with 10-6 M OT markedly enhanced the MOR signaling induced by 10-6 M endomorphin-1, β-endorphin, morphine, fentanyl, and DAMGO. Moreover, in the competitive receptor-binding assay, 10-6 M OT did not alter the affinity of endomorphin-1 or morphine for MOR. These results suggest that OT could function as a positive allosteric modulator that regulates the efficacy of MOR signaling, and thus OT might represent a previously unrecognized candidate analgesic agent.

BACKGROUND: Adjuvant chemotherapy with S-1 for resected pancreatic cancer demonstrated survival benefits compared with gemcitabine in the JASPAC 01 trial. We investigated the effect of these agents on health-related quality of life (HRQOL) of patients in the JASPAC 01 trial. METHODS: Patients with resected pancreatic cancer were randomly assigned to receive gemcitabine (1000 mg/m2 weekly for three of four weeks for up to six cycles) or S-1 (40, 50, or 60 mg twice daily for four of six weeks for up to four cycles). HRQOL was assessed using the EuroQol-5D-3L (EQ-5D) questionnaire at baseline, months three and six, and every 6 months thereafter. HRQOL end-points included change in EQ-5D index from baseline, responses to five items in the EQ-5D, and quality-adjusted life months up to 24 months. RESULTS: Of randomised 385 patients, 354 patients were included in HRQOL analysis. Mean change in the EQ-5D index was similar in the S-1 and gemcitabine groups within 6 months from treatment initiation (difference, 0.024; P = 0.112), whereas corresponding mean from 12 to 24 months was better in the S-1 group than in the gemcitabine group (difference, 0.071; P < 0.001). Problems in mobility and pain/discomfort were also less frequent in the S-1 group than in the gemcitabine group in that period. Quality-adjusted life months were longer in the S-1 group than in the gemcitabine group (P < 0.001). CONCLUSION: Adjuvant chemotherapy with S-1 does not improve HRQOL within 6 months from treatment initiation but does improve HRQOL thereafter and quality-adjusted life months. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000000655 at UMIN CTR.

Despite recent advances in chemotherapy, outcomes of patients with peritoneal metastases (PM) from gastric cancer are still very poor and standard treatment has not been established. Although oral S-1 appears to be effective for patients with PM, the effects of systemic chemotherapy are limited. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) yield fewer benefits in patients with PM from gastric cancer than in patients with PM from other malignancies. In comparison, repeated intraperitoneal chemotherapy (RIPEC) with taxanes using an implantable peritoneal access port has a pharmacokinetic advantage for the control of peritoneal lesions and in combination with systemic chemotherapy can result in surprisingly long-term survival in patients with PM from gastric cancer. Herein, we review the results of recent clinical studies specifically targeting PM from gastric cancer and discuss future prospects for an intraperitoneal approach to the ideal treatment of patients with gastric cancer with peritoneal involvement.

Many types of immune cells appear in peritoneal cavity after abdominal surgery. In patients who underwent laparotomy due to gastric cancer, peritoneal lavages were obtained before and after surgical procedure. Cells were recovered from intermediate layer after Ficoll-Hypaque centrifugation and analyzed for phenotypes and functions, especially focused on low density neutrophils (LDN). The number of CD66b (+) LDN with mature phenotype was markedly elevated in postoperative as compared with preoperative lavages. Short term culture of the purified LDN produced many threadlike structures positive for SYTOX, nucleic acid staining, as well as histone and myeloperoxidase, suggesting the NETs formation. Human gastric cancer cells, MKN45, OCUM-1 and NUGC-4, were selectively attached on the NETs, which was totally abolished by the pretreatment of DNAse I. Intraperitoneal (IP) co-transfer of the LDN with MKN45 in nude mice strongly augments the metastasis formation on peritoneum, which was strongly suppressed by the following IP administration of DNAse I. Many NETs-like structures were detected on the surface of human omental tissue resected by gastrectomy. NETs on peritoneal surface can assist the clustering and growth of free tumor cells disseminated in abdomen. Disruption of the NETs by DNAse might be useful to prevent the peritoneal recurrence after abdominal surgery.

Purpose To evaluate the association between tumor shrinkage patterns shown with magnetic resonance (MR) imaging during neoadjuvant chemotherapy (NAC) and prognosis in patients with low-grade luminal breast cancer. Materials and Methods This retrospective study was approved by the institutional review board and informed consent was obtained from all subjects. The low-grade luminal breast cancer was defined as hormone receptor-positive and human epidermal growth factor receptor 2-negative with nuclear grades 1 or 2. The patterns of tumor shrinkage as revealed at MR imaging were categorized into two types: concentric shrinkage (CS) and non-CS. Among 854 patients who had received NAC in a single institution from January 2000 to December 2009, 183 patients with low-grade luminal breast cancer were retrospectively evaluated for the development set. Another data set from 292 patients who had received NAC in the same institution between January 2010 and December 2012 was used for the validation set. Among these 292 patients, 121 patients with low-grade luminal breast cancer were retrospectively evaluated. Results In the development set, the median observation period was 67.9 months. Recurrence was observed in 31 patients, and 16 deaths were related to breast cancer. There were statistically significant differences in both the disease-free survival (DFS) and overall survival (OS) rates between patterns of tumor shrinkage (P < .001 and P < .001, respectively). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .001) and OS (P = .009) rate. In the validation set, the median follow-up period was 56.9 months. Recurrence was observed in 20 patients (16.5%) and eight (6.6%) deaths were related to breast cancer. DFS rate was significantly longer in patients with the CS pattern (72.8 months; 95% confidence interval [CI]: 69.9, 75.6 months) than in those with the non-CS pattern (56.0 months; 95% CI: 49.1, 62.9 months; P ≤ .001). The CS pattern was associated with an excellent prognosis (median OS, 80.6 months; 95% CI: 79.3, 81.8 months vs 65.0 months; 95% CI: 60.1, 69.8 months; P = .004). Multivariate analysis demonstrated that the CS pattern had the only significant independent association with DFS (P = .007) and OS (P = .037) rates. Conclusion The CS pattern as revealed at MR imaging during NAC had the only significant independent association with prognosis in patients with low-grade luminal breast cancer. © RSNA, 2017.

The initial management of patients with suspected acute biliary infection starts with the measurement of vital signs to assess whether or not the situation is urgent. If the case is judged to be urgent, initial medical treatment should be started immediately including respiratory/circulatory management if required, without waiting for a definitive diagnosis. The patient's medical history is then taken; an abdominal examination is performed; blood tests, urinalysis, and diagnostic imaging are carried out; and a diagnosis is made using the diagnostic criteria for cholangitis/cholecystitis. Once the diagnosis has been confirmed, initial medical treatment should be started immediately, severity should be assessed according to the severity grading criteria for acute cholangitis/cholecystitis, and the patient's general status should be evaluated. For mild acute cholangitis, in most cases initial treatment including antibiotics is sufficient, and most patients do not require biliary drainage. However, biliary drainage should be considered if a patient does not respond to initial treatment. For moderate acute cholangitis, early endoscopic or percutaneous transhepatic biliary drainage is indicated. If the underlying etiology requires treatment, this should be provided after the patient's general condition has improved; endoscopic sphincterotomy and subsequent choledocholithotomy may be performed together with biliary drainage. For severe acute cholangitis, appropriate respiratory/circulatory management is required. Biliary drainage should be performed as soon as possible after the patient's general condition has been improved by initial treatment and respiratory/circulatory management. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also included.

INTRODUCTION: Duodenal gastrointestinal tumors (GISTs) are rare. Duodenal GISTs and pancreatic neuroendocrine tumors (NETs) may appear similar on imaging studies. GISTs arising from the second or third portions of duodenum may be incorrectly diagnosed as pancreatic NETs. PRESENTATION OF CASE: The patient is a 79-year-old man who was referred to our hospital with a history of tarry stools and loss of consciousness. Urgent upper digestive tract endoscopy revealed a bleeding submucosal duodenal lesion, which was controlled using endoscopic clips. Enhanced computed tomography scan showed a hyper-vascular mass 50 mm in diameter, at the pancreatic uncus. The patient underwent a pylorus-preserving pancreaticoduodenectomy. Histologically, the tumor was composed of spindle-shaped cells immunohistochemically positive for c-kit and CD34, and the lesion diagnosed as a duodenal GIST. DISCUSSION: Duodenal GISTs often present with gastrointestinal bleeding, which can necessitate emergency surgery. Surgical resection with regional lymph node dissection is the optimal treatment for pancreatic NETs. In contrast, GISTs are generally treated with a minimal resection and without lymph node dissection. Thus, establishing the diagnosis is important in the management of these tumors. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is effective to establish the diagnosis of these lesions. CONCLUSION: A tumor located in the pancreatic head or mesenteric side of the duodenum cannot always be diagnosed based on imaging, and is ideally diagnosed histologically to guide the extent of resection. While EUS-FNA can establish the diagnosis, the complications of this procedure must be considered.

We report a unique case of a 74-old man, who presented with double cancers, showing metastasis of pancreatic cancer to colon cancer. Histopathological examination after surgery revealed that the patient had ascending colon cancer, which metastasized to the liver (pT4N0M1), as well as pancreatic cancer (pT2N1M1) that metastasized to the most invasive portion of the colon cancer, namely the serosal to subserosal layers. Although the mechanisms for this scenario have yet to be elucidated, we speculate that the metastatic pancreatic carcinoma overtook the stromal microenvironment of the colon cancer. Namely, the cancer microenvironment enriched by cancer-associated fibroblasts, which supported the colon cancer, might be suitable for the invasion and engraftment by pancreatic carcinoma. The similarity of histological appearance might make it difficult to distinguish metastatic pancreatic carcinoma within colon cancer. Furthermore, the metastasis of pancreatic carcinoma in colon carcinoma might be more common, despite it not having been previously reported.

INTRODUCTION: Black adrenal adenoma (BAA) is a rare, benign adrenal lesion with a black or brown appearance. This is the first report of this lesion in a patient with a synchronous esophageal cancer and highlights the importance of considering a false positive finding on a Positron Emission Tomography (PET) scan, which might otherwise preclude resection. PRESENTATION OF CASE: A 73-year-old male was diagnosed with mid-esophagus carcinoma. Computed tomography scan revealed an enlarged left adrenal gland. Plasma adrenocorticotropic hormones levels were normal. To characterize the adrenal lesion, a PET scan was obtained which showed high uptake of 18F-fluoro-2-deoxy-d-glucose (FDG), consistent with a metastasis, suggesting T3N2M1, clinical stage IV esophageal cancer. After two courses of neo-adjuvant therapy, sub-total esophagectomy and left adrenalectomy were performed. The adrenal tumor was soft, and black in color, diagnosed as a BAA on histology. The pathologic stage of the esophageal cancer was T3N0M0, Stage II. Six months after surgery, he is alive without recurrence. DISCUSSION: High FDG uptake by an adrenal lesion on PET scan, as in this patient, usually suggests a metastatic lesion. Although rare, patients with esophageal cancer and adrenal metastases have been reported to have long-term survival, so it is important to characterize an adrenal lesion when found. CONCLUSION: Most adrenal lesions with high FDG uptake are malignant, but BAA is also positive on PET scan. Although rare, BAA should be considered in patients with solitary adrenal lesions with high uptake on PET scan, even in the presence of a malignancy.

INTRODUCTION: Gastric leiomyomas are benign mesenchymal tumors, comprising about 2.5% of gastric neoplasms, which can be difficult to differentiate from gastrointestinal stromal tumors which have malignant potential. Granular cell tumors in the abdominal wall are also rare. Since mesenchymal tumors are difficult to diagnose by imaging, further studies are needed to establish the diagnosis. PRESENTATION OF CASE: A 60-year-old asymptomatic woman underwent routine upper endoscopy and was found to have a gastric submucosal lesion. Computed tomography scan also showed an abdominal wall mass. The appearance of both lesions on imaging studies were similar, but it was unclear if the two lesions had the same origin. Endoscopic ultrasound-guided fine needle aspiration biopsy of the gastric lesion was insufficient to establish the diagnosis. Laparoscopic-endoscopic cooperative resection of the gastric lesion and ultrasound-guided core-needle biopsy of the abdominal wall mass enabled pathological diagnosis of both lesions. DISCUSSION: Diagnostic imaging findings of these two lesions were similar. Histologic and immunohistochemical studies are essential to establish a definitive diagnosis. Laparoscopic-endoscopic cooperative surgery may be an effective minimally invasive approach, allowing both pathological diagnosis and complete resection of a gastric submucosal tumor, especially when endoscopic-ultrasound guided fine needle aspiration or biopsy fails to make the diagnosis. CONCLUSION: Laparoscopic-endoscopic cooperative surgery can be an effective minimally invasive approach to resect some lesions. This is first report of the patient with a synchronous gastric leiomyoma and an intramuscular granular cell tumor in the abdominal wall.

BACKGROUND: This study aimed to compare the detection of bone metastases from breast cancer on F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and bone scintigraphy (BS). An explorative search for factors influencing the sensitivity or uptake of BS and FDG-PET was also performed. METHODS: Eighty-eight patients with bone metastases from breast cancer were eligible for this study. Histological confirmation of bone metastases was obtained in 31 patients. The bone metastases were visually classified into four types based on their computed tomography (CT) appearance: osteoblastic, osteolytic, mixed, and negative. The sensitivity of BS and FDG-PET were obtained regarding CT type, adjuvant therapy, and the primary tumor characteristics. The FDG maximum standardized uptake value (SUVmax) was analyzed. RESULTS: The sensitivities of the three modalities (CT, BS, and FDG-PET) were 77, 89, and 94%, respectively. The sensitivity of FDG-PET for the osteoblastic type (69%) was significantly lower than that for the other types (P < 0.001), and the sensitivity of BS for the negative type (70%) was significantly lower than that for the others. Regarding tumor characteristics, the sensitivity of FDG-PET significantly differed between nuclear grade (NG)1 and NG2-3 (P = 0.032). The SUVmax of the osteoblastic type was significantly lower than that of the other types (P = 0.009). The SUVmax of NG1 was also significantly lower than that of NG2-3 (P = 0.011). No significant difference in FDG uptake (SUVmax) was detected between different histological types. CONCLUSION: Although FDG-PET is superior to BS for the detection of bone metastases from breast cancer, this technique has limitations in depicting osteoblastic bone metastases and NG1.

Metachronous solitary metacarpal bone metastasis from rectal cancer has not been reported previously. Here, we describe a 54-year-old woman who underwent abdominoperineal resection for rectal cancer following neoadjuvant chemoradiotherapy. The resected specimen contained adenocarcinoma with no lymph node metastases (Stage II, T3N0M0); no adjuvant chemotherapy was administered. Fifteen months after surgery, the patient presented with pain and swelling of the right thumb. Radiography revealed metacarpal bone destruction, and fluorine-18 fluorodeoxyglucose positron emission tomography showed uptake only in the metacarpal bone. Open biopsy revealed an adenocarcinoma, and a right thumb resection was performed. Histological examination indicated features of adenocarcinoma similar to the findings of a rectal lesion, leading to a diagnosis of metachronous solitary metacarpal bone metastasis from rectal cancer. The patient remains free of disease after 6 years of follow-up. Our findings suggest that surgical resection may lead to favorable outcomes in patients with resectable solitary bone metastases.

Bile duct injury (BDI) during laparoscopic cholecystectomy remains a serious iatrogenic surgical complication. BDI most often occurs as a result of misidentification of the anatomy; however, clinical evidence on its precise mechanism and surgeons' perceptions is scarce. Surgeons from Japan, Korea, Taiwan, and the USA, etc. (n = 614) participated in a questionnaire regarding their BDI experience and near-misses; and perceptions on landmarks, intraoperative findings, and surgical techniques. Respondents voted for a Delphi process and graded each item on a five-point scale. The consensus was built when ≥80% of overall responses were 4 or 5. Response rates for the first- and second-round Delphi were 60.6% and 74.9%, respectively. Misidentification of local anatomy accounted for 76.2% of BDI. Final consensus was reached on: (1) Effective retraction of the gallbladder, (2) Always obtaining critical view of safety, and (3) Avoiding excessive use of electrocautery/clipping as vital procedures; and (4) Calot's triangle area and (5) Critical view of safety as important landmarks. For (6) Impacted gallstone and (7) Severe fibrosis/scarring in Calot's triangle, bail-out procedures may be indicated. A consensus was reached among expert surgeons on relevant landmarks and intraoperative findings and appropriate surgical techniques to avoid BDI.